We plan to study in some detail the thyroid gland physiology as it pertains to the two areas: (i) the relative significance of 3,3',5'- triiodothyronine (reverse T3, rT3), 3,3',5-triiodothyronine (T3) and thyroxine (T4) in health and disease and (ii) the hypothalamo- hypophyseal-thyroid axis in Graves' disease. In (i) we shall use the new radioimmunoassay (RIA) of rT3 and recently introduced RIAs of T3 and T4 to study: (1) the relative concentrations of rT3, T3, and T4 in health and disease, including situations where serum T3 is known to be low e.g. term fetus, chronic illness, hepatic cirrhoses, etc., (2) the relative contribution of thyroid and peripheral tissues to the daily turnover of rT3; (3) the rT3-binding characteristics of serum and tissue proteins; (4) the factors which may influence the conversion of T4 to rT3 and T3; (5) the inter-relationship between conversion of T4 to T3 and that to rT3; (6) the relative effects of administration of TSH or thyrotropin-releasing hormone (TRH) on serum rT3, T3 and T4. In (ii) we shall use the TRH stimulation test to study: (1) whether the previously reported two kinds of abnormal (subnormal and supranormal) serum TSH responses to TRH in euthyroid patients with Graves' ophthalmopathy represent different stages of Graves' disease or two types of the disease; (2) the pattern of serum TSH response to TRH in Graves' disease patients previously hyperthyroid but rendered euthyroid by various treatments; (3) the effect of acute administration of glucocorticoids on serum T3, T4, thyroglobulin, LATS and HTS in Graves' disease.